Persistence with denosumab and zoledronic acid among older women: a population-based cohort study

Persistence to denosumab or zoledronic acid was increased compared to oral bisphosphonates.

Denosumab and zoledronic acid are alternative therapies to oral bisphosphonates. Few studies have assessed persistence of those agents.

Incident users of denosumab and zoledronic acid were identified using healthcare databases of public drug insurance plan of Quebec province, Canada. Patients initiating therapy between October 1, 2008, and June 30, 2013, and aged 50 years and over were eligible. A persistence rate was assessed over a 2-year period. We assess the proportion of patients receiving the second, third, and fourth injections within a specific delay of predicted time of renewal of both agents. The predictors of non-persistence were analyzed using a Cox regression model only among women.

Among 12,689 incident users, 97.2 % were women. Kaplan–Meier analysis showed a slow decline of persistence after initiating zoledronic acid compared to denosumab therapy, dropping to 81.6 and 63.3 % after 1 and 2 years of follow-up using the permissive gaps of 56 days, in contrast to zoledronic acid, where persistence rate still stays at 74.8 % after 2 years of follow-up using the permissive gap of 112 days. The likelihood of non-persistence was significantly higher among new users of denosumab and zoledronic acid among older patients and year of initiation; but depression and diabetes are only predictors of non-persistence among the zoledronic group. Concomitant use of calcium and vitamin D supplements was at low level which may compromise the clinical efficacy.

The persistence rate to denosumab and zoledronic acid was higher to the published data of oral bisphosphonates. The second intention of treatment seems to target more severe patients which may more likely to be compliant.